Molecular Regulation Of CRH Gene Expression In The Human Placenta
Funder
National Health and Medical Research Council
Funding Amount
$70,285.00
Summary
Approximately 70% of infant death is a result of premature birth. Preterm delivery occurs in 6-10% of pregnancies, and there has been no reduction in this rate in the last 30 years. This is largely because we remain ignorant of how normal and preterm birth is controlled. Understanding the physiology of human pregnancy is a critical step in the development of ways to detect and prevent preterm birth. Our group has demonstrated a link between production of a hormone (corticotropin releasing hormon ....Approximately 70% of infant death is a result of premature birth. Preterm delivery occurs in 6-10% of pregnancies, and there has been no reduction in this rate in the last 30 years. This is largely because we remain ignorant of how normal and preterm birth is controlled. Understanding the physiology of human pregnancy is a critical step in the development of ways to detect and prevent preterm birth. Our group has demonstrated a link between production of a hormone (corticotropin releasing hormone, CRH) in the placenta and the length of time the baby is carried in the mother. In women who will deliver prematurely the rise in CRH production occurs earlier and more rapidly, while in women who deliver late the rise occurs more slowly. This work has led to the concept of a biological clock that determines the length of time the fetus will be carried by the mother before birth, and in which production of CRH in the placenta plays a central role. We have been studying how the CRH gene is controlled in placental cells. We have discovered some regions in the DNA of the CRH gene which have important roles in controlling how much CRH is made by the placenta. The experiments described in this project will determine the molecular mechanisms that control the production of CRH in the human placenta. This will be done by examining the DNA sequences involved in controlling the CRH gene and by identifying the proteins that actually perform the regulating functions that result in either increased or decreased amounts of CRH being produced by the placenta. This important information will help us better understand how normal and preterm birth is controlled, and from that knowledge new ways to detect and prevent premature birth can be developed.Read moreRead less
Novel sources of nitric oxide (NO) in cells: Implications for an endocrine role for NO. Communication between cells is essential for coordinating and controlling a healthy body. A key regulator and cell-communicating molecule is the gas, nitric oxide. Although nitric oxide is a simple substance we still do not fully understand all aspects of its cellular functions. It is assumed that nitric oxide is synthesised in the body and, after release, is rapidly metabolized and eliminated. Reductions in ....Novel sources of nitric oxide (NO) in cells: Implications for an endocrine role for NO. Communication between cells is essential for coordinating and controlling a healthy body. A key regulator and cell-communicating molecule is the gas, nitric oxide. Although nitric oxide is a simple substance we still do not fully understand all aspects of its cellular functions. It is assumed that nitric oxide is synthesised in the body and, after release, is rapidly metabolized and eliminated. Reductions in the levels of nitric oxide in the body are associated with several diseases states and states of dysfunction including cardiovascular disease, diabetes and also impotence. Professor Triggle's study seeks to characterize how tissues may store nitric oxide, thus prolonging the life of nitric oxide, and how such stores are released. Read moreRead less
Alpha-2-Macroglobulin And The Transport And Uptake Of The Hormone, Hepcidin
Funder
National Health and Medical Research Council
Funding Amount
$533,541.00
Summary
Hepcidin is a peptide hormone that is a major regulator of iron metabolism. It has been suggested that hepcidin is free in the blood. However, we recently identified that hepcidin binds with alpha-2-macroglobulin (a2-M) in the plasma and this increases the efficacy of this peptide. The demonstration that a2-M plays a role in hepcidin biology will lead to a better understanding of hepcidin physiology, the development of methods for its measurement and improved treatment of iron related diseases.
Establishing evidence for the functional properties of a whole grain in weight management. The successful development of functional foods relies on communicating proven effects. This project aims to prove that the food containing the satiety properties of a whole grain (OG) may help in weight management. We will conduct basic research investigating the link between consumption of OG-containing foods and the regulatory mechanisms of satiety, and test whether the satiety properties can be used to ....Establishing evidence for the functional properties of a whole grain in weight management. The successful development of functional foods relies on communicating proven effects. This project aims to prove that the food containing the satiety properties of a whole grain (OG) may help in weight management. We will conduct basic research investigating the link between consumption of OG-containing foods and the regulatory mechanisms of satiety, and test whether the satiety properties can be used to prevent, reduce and correct body weight gain in the early, middle and late stages of obesity. We will then apply this understanding in a human trial of mildly and long term overweight subjects, to aid the formulation of statements on the potential health benefits from consuming OG.Read moreRead less
Single minded 1 in neuron development and satiety signalling. An understanding of how Single minded 1 (SIM1) regulates target genes may allow new pharmaceutical approaches to be designed to combat obesity. As Sim1 belongs to a family of closely related gene regulatory proteins which function in early development and homeostasis, deciphering the molecular control mechanisms of Sim1 may help understand how the related factors function in processes such as angiogenesis, response to low oxygen stres ....Single minded 1 in neuron development and satiety signalling. An understanding of how Single minded 1 (SIM1) regulates target genes may allow new pharmaceutical approaches to be designed to combat obesity. As Sim1 belongs to a family of closely related gene regulatory proteins which function in early development and homeostasis, deciphering the molecular control mechanisms of Sim1 may help understand how the related factors function in processes such as angiogenesis, response to low oxygen stress, invasion of environmental pollutants and autism spectrum diseases. The ability to manipulate these factors would be of great benefit in treating a range of disorders, but a thorough molecular understanding of these factors needs be obtained prior to attempting design of pharmaceuticals.Read moreRead less
Gene therapy for islet transplantation. Improved understanding of aetiology of type I diabetes. Development of islet transplantation as a clinical therapeutic for type I diabetes. Improved efficacy of islet transplantation. Improved health for subjects with type I diabetes. Decreased diabetic complications. Improved quality of life for subjects with type I diabetes. Reduced burden on health system for management of diabetic complications for subjects with type I diabetes
Development of natural herbal medicines for managing metabolic syndrome in order to prevent type 2 diabetes. Type 2 diabetes affects almost 7% of Australia~{!/~}s population. Its incidence continues to grow, as indicated by high rates of metabolic syndrome, a pre-stage of type 2 diabetes. Using novel and bio-molecular techniques, we will evaluate the effects and mechanisms of three natural compounds from anti-diabetic Chinese herbs on cellular and rodent models with metabolic syndrome. This stud ....Development of natural herbal medicines for managing metabolic syndrome in order to prevent type 2 diabetes. Type 2 diabetes affects almost 7% of Australia~{!/~}s population. Its incidence continues to grow, as indicated by high rates of metabolic syndrome, a pre-stage of type 2 diabetes. Using novel and bio-molecular techniques, we will evaluate the effects and mechanisms of three natural compounds from anti-diabetic Chinese herbs on cellular and rodent models with metabolic syndrome. This study will provide scientific evidence as to how and why herbal compounds improve insulin resistance and abnormalities in glucose and lipids metabolism. The outcome of this project will support the development of natural products to manage metabolic syndrome and prevent type 2 diabetes.
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Ultrasound in muscle vascular research, and gene therapy. This project focuses on ultrasound and microbubbles for the imaging of microvascular blood flow patterns in skeletal muscle and as a modality for drug delivery. The aim is to develop and refine technology specifically for (i) assessment of muscle microvascular flow in health and disease, and for (ii) delivery of state-of-the art gene constructs to endothelial cells that control blood flow in the muscle microvasculature. We anticipate impr ....Ultrasound in muscle vascular research, and gene therapy. This project focuses on ultrasound and microbubbles for the imaging of microvascular blood flow patterns in skeletal muscle and as a modality for drug delivery. The aim is to develop and refine technology specifically for (i) assessment of muscle microvascular flow in health and disease, and for (ii) delivery of state-of-the art gene constructs to endothelial cells that control blood flow in the muscle microvasculature. We anticipate improved technology for early diagnosis of impairment in microvascular flow relevant to muscle insulin resistance and novel therapeutics that improve muscle microvascular blood flow applicable to the treatment of diabetes.Read moreRead less
Identifying novel roles of disease-related proteins in the regulation of exocytosis and nervous communication. This research aims to identify new molecules involved in regulating nerve communication and hormone secretion and which are relevent to human diseases and conditions including Type 2 Diabetes, Down Syndrome, Alzheimer's Disease and Huntington's Disease. The findings may provide new targets in the treatments of such conditions. This research is therefore of special relevance to National ....Identifying novel roles of disease-related proteins in the regulation of exocytosis and nervous communication. This research aims to identify new molecules involved in regulating nerve communication and hormone secretion and which are relevent to human diseases and conditions including Type 2 Diabetes, Down Syndrome, Alzheimer's Disease and Huntington's Disease. The findings may provide new targets in the treatments of such conditions. This research is therefore of special relevance to National Research Priority 2: Promoting and Maintaining Good Health and especially to the sub-areas of this Research Priority 2: Ageing well, ageing productively and Preventative healthcare.Read moreRead less
Estrogen signalling in gonadotropes. Estrogen action is a normal prerequisite for cyclic function of reproduction in the female, but little is known about how this important hormone acts in the relevant cells of the pituitary gland (gonadotropes). In order to gain information on normal function, we will conduct studies on gonadotropes treated with estrogen in a range of paradigms. The information will be valuable in understanding normal reproduction, but will also form the basis of further studi ....Estrogen signalling in gonadotropes. Estrogen action is a normal prerequisite for cyclic function of reproduction in the female, but little is known about how this important hormone acts in the relevant cells of the pituitary gland (gonadotropes). In order to gain information on normal function, we will conduct studies on gonadotropes treated with estrogen in a range of paradigms. The information will be valuable in understanding normal reproduction, but will also form the basis of further studies to investigate the effects of drugs that affect estrogen action and environmental estrogens. Read moreRead less